Clearing the Confusion on the Role of the ‘Male’ Hormones in Breast Cancer

Associate Professor Elgene Lim

Estrogen receptor positive (ER+) breast cancer is the most common form of the disease, in which cancer cells grow in response to the estrogen hormone. Estrogen, and another hormone called progesterone, are often referred to as “female” hormones. Their connection with breast cancer has been well documented. However, there is controversy on the role of the so-called “male” hormones, known as androgens, in breast cancer.

The androgen receptor (AR) protein is expressed in over 75% of hormonal breast cancers.  In prostate cancer, targeting and blocking the AR protein has been a successful treatment option, but whether a similar approach can be taken in breast cancer is unclear. Until now, there has been controversy as to whether we should try to activate or block the AR protein in people with breast cancer.

Associate Professor Elgene Lim is a National Breast Cancer Foundation Endowed Chair based at the Garvan Institute of Medical Research in Sydney. He is concerned that the controversy is impacting the development of new treatments for hormone-related breast cancer.

“There is confusion on whether it is best to stimulate or inhibit the role of AR in endocrine resistant breast cancer (cancers that have become resistant to treatment that stops estrogen and progesterone from helping tumours to grow), largely because the preclinical modelling up to now has been suboptimal,” Associate Professor Lim explained. “This confusion has resulted in clinical trials being conducted simultaneously with drugs that either stimulate or inhibit AR activity.”

New research by Associate Professor Lim and his colleagues will now provide further clarity on this issue. The recent NBCF-funded study identified the components of AR signaling that contribute to hormone-related cancer, helping to provide better evidence for the choice of treatment drugs.

The study investigated a drug called enzalutamide, which is an AR inhibitor that has been used successfully for treatment of prostate cancer, and also utilised other techniques to dissect the role of AR in endocrine resistant breast cancer. Their study showed that while enzalutamide was not effective at treating endocrine resistant breast cancer. However, the study has identified other components of AR function that could result in anti-tumour activity. This provides new potential treatment alternatives, which will now be investigated in further research studies.

“Our work will provide the critical preclinical rationale for the most effective way to target the AR, a commonly expressed protein, in breast cancer,” said Associate Professor Lim. “This is an area of clinical need, as while current endocrine therapies are effective, approximately 30% of patients will have their cancer recur in spite of treatment.”

The study was recently published in the journal Endocrine-Related Cancer and was funded by the National Breast Cancer Foundation in conjunction with Cancer Australia.